DESCRIPTION: This application has 4 specific aims. 1) To identify amino acids responsible for the A2 domain's association with thrombin-activated VIIIa, and if possible to engineer a human F.VIII with increased specific activity. 2) To identify BiP binding sites within the A1 domain, and to determine the role of BiP binding in protein folding. 3) To determine the reasons for the low level of F.VIII MRNA expression in transfected cells. These 3 aims will all be accomplished by the use of recombinant proteins produced in either transient or stable expression systems, and analyzed using standard molecular and biochemical techniques. The goal of the 4th aim is to determine, using a porcine model of von Willebrand's disease, whether VWF specifically affects F.VIII MRNA or protein expression in vivo.